Kids may have higher risk of death long after allo-HSCT

Photo from UAB

Children may have an increased risk of premature death decades after allogeneic hematopoietic stem cell transplant (allo-HSCT), according to a study published in JAMA Oncology.

The leading causes of death in the patients studied were infection and chronic graft-vs-host disease (GVHD), patients’ primary disease, and subsequent cancers.

“This study shows that, while we are able to save the life of the child during their cancer treatment, we need to continue to provide proactive follow-up care with these types of patients throughout the rest of their life, as they are still an at-risk population,” said study author Smita Bhatia, MBBS, of the University of Alabama at Birmingham (UAB).

“The high intensity of therapeutic exposures at a young age lends itself to cause morbidities and organ compromise once they reach adulthood.”

Dr Bhatia and her colleagues conducted this retrospective study of children who underwent allo-HSCT between January 1, 1974, and December 31, 2010, and were followed until December 31, 2016.

The study included 1388 patients who lived 2 years or more after transplant. Their median age at transplant was 14.6 years (range, 0-21). The majority of patients were non-Hispanic white (70.7%), and most were male (59.7%).

Patients underwent allo-HSCT to treat acute lymphoblastic leukemia (ALL, 25.1%), acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS, 23.5%), inborn errors of metabolism (13.8%), severe aplastic anemia (SAA, 10.6%), Fanconi anemia (8.3%), chronic myelogenous leukemia (CML, 6.5%), immune disorders (4%), sickle cell disease or thalassemia (1.9%), and other diseases.

Most patients had a related donor (57.9%), and most received a bone marrow transplant (73.4%).

The most common component of conditioning was cyclophosphamide (80.5%), followed by total body irradiation (TBI, 64.3%). About half of patients (49.8%) received both cyclophosphamide and TBI, and nearly a quarter (23.5%) received busulfan and cyclophosphamide.

Outcomes

The researchers found that allo-HSCT recipients had a 14.4-fold greater risk of premature death than the general population.

The team said the absolute excess risk of all-cause mortality was 12.0 per 1000 person-years, and relative mortality remained elevated 25 years or more after transplant (standardized mortality ratio, 2.9).

At a median follow-up of 14.9 years (range, 2.0 to 41.2), 295 patients had died. The 20-year overall survival rate was 79.3%.

The cause of death was available for 82.7% of patients (244/295), and some of these patients had more than 1 cause listed. Causes of death included:

• Infection and/or chronic GVHD—49.6%
• Primary disease—24.6%
• Subsequent malignant neoplasm—18.4%
• Cardiac disease—9.8%
• Pulmonary disease—7.8%
• External causes—2.9%
• Other causes—18.0%.

The hazard of all-cause late mortality was higher among patients who were older at transplant (hazard ratio [HR], 1.03; P=0.004) and those who had a high risk of relapse at transplant (HR, 1.95; P<0.001).

Compared to patients treated for ALL, the hazard of all-cause late mortality was lower among patients with AML/MDS (HR, 0.72; P=0.04), CML (HR, 0.53; P=0.02), Fanconi anemia (HR, 0.49; P=0.03), immune disorders (HR, 0.32; P=0.006), and SAA (HR, 0.33; P<0.001).

The hazard of all-cause late mortality was lower for patients who received conditioning with busulfan and cyclophosphamide (HR, 0.62; P=0.03) than for those who received TBI and cyclophosphamide.

Compared to patients treated for ALL, the hazard of relapse-related mortality was lower among patients with AML/MDS (HR, 0.39; P=0.01) and SAA (HR, 0.09; P=0.03), and the hazard of non-relapse mortality was lower for patients with SAA (HR, 0.36; P=0.004) and immune disorders (HR, 0.14; P=0.009).

The hazard of non-relapse mortality was higher for patients who were older at transplant (HR, 1.03; P=0.03), patients who received peripheral blood stem cells rather than bone marrow (HR, 2.39; P=0.01), and patients who had a high risk of relapse at transplant (HR, 2.05; P<0.001).

Photo from UAB

Children may have an increased risk of premature death decades after allogeneic hematopoietic stem cell transplant (allo-HSCT), according to a study published in JAMA Oncology.

The leading causes of death in the patients studied were infection and chronic graft-vs-host disease (GVHD), patients’ primary disease, and subsequent cancers.

“This study shows that, while we are able to save the life of the child during their cancer treatment, we need to continue to provide proactive follow-up care with these types of patients throughout the rest of their life, as they are still an at-risk population,” said study author Smita Bhatia, MBBS, of the University of Alabama at Birmingham (UAB).

“The high intensity of therapeutic exposures at a young age lends itself to cause morbidities and organ compromise once they reach adulthood.”

Dr Bhatia and her colleagues conducted this retrospective study of children who underwent allo-HSCT between January 1, 1974, and December 31, 2010, and were followed until December 31, 2016.

The study included 1388 patients who lived 2 years or more after transplant. Their median age at transplant was 14.6 years (range, 0-21). The majority of patients were non-Hispanic white (70.7%), and most were male (59.7%).

Patients underwent allo-HSCT to treat acute lymphoblastic leukemia (ALL, 25.1%), acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS, 23.5%), inborn errors of metabolism (13.8%), severe aplastic anemia (SAA, 10.6%), Fanconi anemia (8.3%), chronic myelogenous leukemia (CML, 6.5%), immune disorders (4%), sickle cell disease or thalassemia (1.9%), and other diseases.

Most patients had a related donor (57.9%), and most received a bone marrow transplant (73.4%).

The most common component of conditioning was cyclophosphamide (80.5%), followed by total body irradiation (TBI, 64.3%). About half of patients (49.8%) received both cyclophosphamide and TBI, and nearly a quarter (23.5%) received busulfan and cyclophosphamide.

Outcomes

The researchers found that allo-HSCT recipients had a 14.4-fold greater risk of premature death than the general population.

The team said the absolute excess risk of all-cause mortality was 12.0 per 1000 person-years, and relative mortality remained elevated 25 years or more after transplant (standardized mortality ratio, 2.9).

At a median follow-up of 14.9 years (range, 2.0 to 41.2), 295 patients had died. The 20-year overall survival rate was 79.3%.

The cause of death was available for 82.7% of patients (244/295), and some of these patients had more than 1 cause listed. Causes of death included:

• Infection and/or chronic GVHD—49.6%
• Primary disease—24.6%
• Subsequent malignant neoplasm—18.4%
• Cardiac disease—9.8%
• Pulmonary disease—7.8%
• External causes—2.9%
• Other causes—18.0%.

The hazard of all-cause late mortality was higher among patients who were older at transplant (hazard ratio [HR], 1.03; P=0.004) and those who had a high risk of relapse at transplant (HR, 1.95; P<0.001).

Compared to patients treated for ALL, the hazard of all-cause late mortality was lower among patients with AML/MDS (HR, 0.72; P=0.04), CML (HR, 0.53; P=0.02), Fanconi anemia (HR, 0.49; P=0.03), immune disorders (HR, 0.32; P=0.006), and SAA (HR, 0.33; P<0.001).

The hazard of all-cause late mortality was lower for patients who received conditioning with busulfan and cyclophosphamide (HR, 0.62; P=0.03) than for those who received TBI and cyclophosphamide.

Compared to patients treated for ALL, the hazard of relapse-related mortality was lower among patients with AML/MDS (HR, 0.39; P=0.01) and SAA (HR, 0.09; P=0.03), and the hazard of non-relapse mortality was lower for patients with SAA (HR, 0.36; P=0.004) and immune disorders (HR, 0.14; P=0.009).

The hazard of non-relapse mortality was higher for patients who were older at transplant (HR, 1.03; P=0.03), patients who received peripheral blood stem cells rather than bone marrow (HR, 2.39; P=0.01), and patients who had a high risk of relapse at transplant (HR, 2.05; P<0.001).

Photo from UAB

Children may have an increased risk of premature death decades after allogeneic hematopoietic stem cell transplant (allo-HSCT), according to a study published in JAMA Oncology.

The leading causes of death in the patients studied were infection and chronic graft-vs-host disease (GVHD), patients’ primary disease, and subsequent cancers.

“This study shows that, while we are able to save the life of the child during their cancer treatment, we need to continue to provide proactive follow-up care with these types of patients throughout the rest of their life, as they are still an at-risk population,” said study author Smita Bhatia, MBBS, of the University of Alabama at Birmingham (UAB).

“The high intensity of therapeutic exposures at a young age lends itself to cause morbidities and organ compromise once they reach adulthood.”

Dr Bhatia and her colleagues conducted this retrospective study of children who underwent allo-HSCT between January 1, 1974, and December 31, 2010, and were followed until December 31, 2016.

The study included 1388 patients who lived 2 years or more after transplant. Their median age at transplant was 14.6 years (range, 0-21). The majority of patients were non-Hispanic white (70.7%), and most were male (59.7%).

Patients underwent allo-HSCT to treat acute lymphoblastic leukemia (ALL, 25.1%), acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS, 23.5%), inborn errors of metabolism (13.8%), severe aplastic anemia (SAA, 10.6%), Fanconi anemia (8.3%), chronic myelogenous leukemia (CML, 6.5%), immune disorders (4%), sickle cell disease or thalassemia (1.9%), and other diseases.

Most patients had a related donor (57.9%), and most received a bone marrow transplant (73.4%).

The most common component of conditioning was cyclophosphamide (80.5%), followed by total body irradiation (TBI, 64.3%). About half of patients (49.8%) received both cyclophosphamide and TBI, and nearly a quarter (23.5%) received busulfan and cyclophosphamide.

Outcomes

The researchers found that allo-HSCT recipients had a 14.4-fold greater risk of premature death than the general population.

The team said the absolute excess risk of all-cause mortality was 12.0 per 1000 person-years, and relative mortality remained elevated 25 years or more after transplant (standardized mortality ratio, 2.9).

At a median follow-up of 14.9 years (range, 2.0 to 41.2), 295 patients had died. The 20-year overall survival rate was 79.3%.

The cause of death was available for 82.7% of patients (244/295), and some of these patients had more than 1 cause listed. Causes of death included:

• Infection and/or chronic GVHD—49.6%
• Primary disease—24.6%
• Subsequent malignant neoplasm—18.4%
• Cardiac disease—9.8%
• Pulmonary disease—7.8%
• External causes—2.9%
• Other causes—18.0%.

The hazard of all-cause late mortality was higher among patients who were older at transplant (hazard ratio [HR], 1.03; P=0.004) and those who had a high risk of relapse at transplant (HR, 1.95; P<0.001).

Compared to patients treated for ALL, the hazard of all-cause late mortality was lower among patients with AML/MDS (HR, 0.72; P=0.04), CML (HR, 0.53; P=0.02), Fanconi anemia (HR, 0.49; P=0.03), immune disorders (HR, 0.32; P=0.006), and SAA (HR, 0.33; P<0.001).

The hazard of all-cause late mortality was lower for patients who received conditioning with busulfan and cyclophosphamide (HR, 0.62; P=0.03) than for those who received TBI and cyclophosphamide.

Compared to patients treated for ALL, the hazard of relapse-related mortality was lower among patients with AML/MDS (HR, 0.39; P=0.01) and SAA (HR, 0.09; P=0.03), and the hazard of non-relapse mortality was lower for patients with SAA (HR, 0.36; P=0.004) and immune disorders (HR, 0.14; P=0.009).

The hazard of non-relapse mortality was higher for patients who were older at transplant (HR, 1.03; P=0.03), patients who received peripheral blood stem cells rather than bone marrow (HR, 2.39; P=0.01), and patients who had a high risk of relapse at transplant (HR, 2.05; P<0.001).